The NIH sponsored Diabetes Control and Complications Trial (DCCT study) clearly demonstrates that tight blood glucose control dramatically slows down the onset of the devastating complications of diabetes. However, tightening glucose control increases hypoglycemic episodes by a factor of three, often times during sleep or without warning. Clearly a means of tracking glucose continuously with trend displays and alarm functions is needed to reduce this risk while facilitating tighter control of blood glucose. To this end, Phase I demonstrated an improved long-term subcutaneous glucose sensor. By stabilizing capillary blood supply at the sensor / foreign body capsule interface, using an approach based on material microarchitecture which stimulates formation of granuloma tissue, sensor lifetime has been doubled. Sensor packaging and geometry modifications have also increased the yield of useful sensors and halved the times to sensor startup. We now request Phase II support to build upon this promising approach in continued dog model studies and to begin a feasibility pilot study in human subjects. The Human Subjects Committee of the University of Wisconsin has granted permission to conduct this pilot study contingent on FDA approval of a pending DE application. Furthermore, industry and venture capital support for Phase III appears likely if there is continued progress in the dog model and success in the initial human subjects pilot study. PROPOSED COMMERCIAL APPLICATION: Only cardiovascular disease and cancer cause more death than diabetes. Diabetes is the leading cause of blindness, limb amputation, and kidney failure. If successful, this glucose sensor research opens the possibility of diabetic patients monitoring their tissue glucose concentration as easily as reading a watch. With additional engineering, a successful sensor could control implanted insulin pumps currently under development in other research laboratories to provide an artificial pancreas for the millions of people with this debilitating disease.